We shall initially use in vitro slice preparations from the mouse brain to study thalamocortical interactions in both directions in the visual system, concentrating on cortical areas V1 and V2 and thalamic nuclei LGN and LP. We then propose to develop in vivo preparations to test hypotheses from the in vitro work. We make heavy use of optogenetics in combination with other stimulation paradigms to activate specific pathways and use both single cell recording and current source density analysis to measure responses. We are particularly interested in the role of the two distinct corticothalamic projections. One emanates from layer 6 and feeds back to the thalamic nucleus innervating that area; we hypothesize that its main function is to depress thalamocortical transmission by multiple complementary mechanisms. The other emanates from layer 5 and is organized in a feed forward fashion, innervating thalamic regions that do not innervate its cortical area; we hypothesize that this represents the initiation of a transthalamic, cortico-thalamo-cortical pathway organized in parallel with direct corticocortical projections. Finally, we shall also test he hypothesis that these dual pathways operate in a coincidence detection manner to control information flow. This could provide more general insights regarding cortical functioning, particularly with respect to new evidence that different cortical areas can dynamically cooperate depending on behavioral needs. PUBLIC HEALTH RELEVANCE: We must better understand visual information flow through the first few stages of cortical processing to begin to understand how pathology in these pathways leads to vision loss including defects in cognitive visual functions, such as selective attention and object recognition. This could also lead to insights into disorders such as schizophrenia, which shows deficits in the sort of corticothalamic relationships we propose to study.